Investigating how nuclei communicate to coordinate gene expression

Project title: Investigating how nuclei communicate to coordinate gene expression With technical advances in tissue engineering, genomics, and cell biology we are entering the era of tissue biology. The discoveries resulting from this research hold promises in a wide variety of domains such as personalized drug screening, bio-robotics, regenerative medicine, and cellular agriculture amongst many. A central branch of the tissue biology field is understanding how cells communicate to define tissue architecture. In our group we use skeletal muscle cells as a model for cellular communication. With hundreds of nuclei in one cell, we can explore how nuclei in the same cytoplasm share information. Using an observable and malleable muscle in vitro system, we will monitor if myonuclei from the same cell coordinate their expression and if this is reflected in their chromatin architecture. This will be achieved by RNA sequencing and image-based spatial transcriptomics. Genes that display synchronized expression will be temporally resolved by developing MS-2 tagging strategies to observe transcriptional bursting. Finally, we will delve into the mechanisms underlying this internuclear coordination by manipulating nuclear positioning and the cytoskeleton. Overall, this project aims to lay new foundations of how cells coordinate and work together towards building complex tissues. The next stage of this work will be to investigate how muscle cells and other cell types (neurons, blood vessels and stem cells) interact to form cell-cell interfaces. More info about the lab at: www.romanlab.org